Investigating the cytological mechanisms of paclitaxel-recombinant hirudin interventional coating to prevent restenosis via NF-κB and Notch-1 pathways
10.3969/j.issn.1004-8812.2024.10.005
- VernacularTitle:从NF-κB和Notch-1通路探索紫杉醇-重组水蛭素介入涂层抗再狭窄的细胞学机制
- Author:
Ting WANG
1
;
Yuan-Shan XU
;
Hong-Mei LI
Author Information
1. 北京中医药大学生命科学学院,北京 100029
- Keywords:
Paclitaxel-recombinant hirudin interventional coating;
Anti restenosis;
NF-κB and Notch-1 pathways;
Cytological mechanisms;
Microregulation
- From:
Chinese Journal of Interventional Cardiology
2024;32(10):576-587
- CountryChina
- Language:Chinese
-
Abstract:
Objective Investigating how the intervention coating composite of paclitaxel-recombinant hirudin(LFN)regulates the connection between Notch-1 and NF-κB pathways to avoid restenosis.Methods Targets and enrichment analysis of LFN anti-ISR were determined using a network-based technique.Human coronary artery smooth muscle cells(HCASMCs)were employed as a model.Lipopolysaccharide(LPS)and Jagged-1 were utilized to activate the Notch-1 and NF-κB pathways in HCASMCs.It is possible to provide light on the relationship between pathway interactions and the growth and migration of HCASMCs by regulating dual pathways.The mechanism of LFN in preventing and curing postoperative restenosis was explained molecularly.Results Computational results revealed that LFN therapy of in-stent restenosis regulated many biological modules.The ideal modeling setting for inflammatory activation of HCASMCs was found to be 1 μg/ml of LPS and Jagged-1 for 24 hours.When compared to the model group,the migration and proliferation changes of modeling-activated HCASMCs were significantly inhibited by LFN(1 μmol/L paclitaxel with 0.2 mg/ml bivalirudin)at the optimal concentration.This resulted in a down-regulation of NF-κB and Notch-1,an up-regulation of IκBα,and a decrease in the expression of NICD,VEGF,MMP2,MMP9,and Bcl-xL.It also down-regulated the expression of OPN,PCNA,Notch-1,and NF-κB(nucleus)and up-regulated the expression of NF-κ B(cytoplasm)(P＜0.05).Among them,the impact of LFN may be directly impacted by changes in Notch-1 and NICD expression.Conclusions LFN prevents restenosis by modulating the Notch-1 and NF-κB pathways and inhibiting the shift of HCASMCs from contractile to synthetic phenotype.
